Why was metformin recalled
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Why Was Metformin Recalled?
Detection of NDMA in Metformin
The primary reason for the recall of metformin was the detection of N-nitrosodimethylamine (NDMA), a potentially carcinogenic impurity, in certain batches of the drug. NDMA is classified as a probable human carcinogen, and its presence in pharmaceuticals is strictly regulated. The acceptable intake (AI) limit for NDMA is set at 96 ng per day. Recalls were initiated when some batches of metformin were found to contain NDMA levels exceeding this limit .
Regulatory Actions and Analysis
International regulatory bodies, including the FDA and the UK Medicines and Healthcare products Regulatory Agency (MHRA), have been actively monitoring and testing metformin products for nitrosamine impurities. Extensive testing of metformin samples from various sources revealed that while the majority of the samples met safety standards, a significant minority contained NDMA above the acceptable limit. Specifically, 17.8% of the finished dosage forms (FDFs) tested had NDMA levels above the AI, prompting recalls to ensure patient safety .
Root Causes of NDMA Formation
Research into the root causes of NDMA formation in metformin has identified several contributing factors. The manufacturing process, particularly the use of water and heat during intra-granulation, and the presence of nitrite and nitrate in excipients, were found to be key factors in the formation of NDMA. Certain excipients, such as hydroxypropyl methyl cellulose (HPMC) and carboxymethyl cellulose sodium, were associated with higher levels of NDMA when combined with water and heat during manufacturing.
Impact and Precautionary Measures
The detection of NDMA in metformin has led to precautionary recalls of affected batches to mitigate potential health risks. Regulatory agencies have advised healthcare professionals to stop supplying the recalled batches and return any remaining stock. Patients are advised to continue taking their medication until they consult with their healthcare provider, as the risk of harm from NDMA at the detected levels is considered low if consumed over a short period.
Conclusion
The recall of metformin was a necessary step to address the presence of NDMA, a potentially harmful impurity. Ongoing regulatory efforts and research aim to understand and mitigate the root causes of NDMA formation in metformin, ensuring the safety and efficacy of this widely used medication.
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